The Cholesterol Conundrum

Why do people on low-cholesterol diets die somewhat less often of heartdisease, yet a lot more often of suicide, accidents, and homicide than the rest of the population?

Although the finding has cropped up in numerous studies over the past decade, it has met with much disbelief in medical circles. Nevertheless, an expert in heart disease research decided to test whether there might be any behavioral basis for the results. His studies link cholesterol in the diet with the neurotransmitter serotonin and its manifestation in impulsive behavior.

Jay Kaplan, Ph.D., looked at monkeys who were eating diets high in fat, but either low or high in cholesterol. After eight months, he found that the low-cholesterol monkeys, who had cholesterol readings of about 220, had no heart disease but were more hostile than the monkeys on a cheeseburger-like diet, whose levels hit 600.

"These monkeys went at it hammer and tong," says Kaplan, a professor of comparative medicine. "They engaged in more contact aggression—highly charged impulsive fighting--than the other monkeys."

Impulsivity, an increasingly scrutinized category of behavior, plays out in violence, suicide, and risk taking. And, impulsive people are likely to have a deficit of serotonin. "People in cholesterol-lowering trials might have been experiencing impulsivity, which led to the higher rates of suicide and accidents," suggests Kaplan.

He then measured serotonin levels in the monkeys' cerebrospinal fluid. Sure enough, the low-cholesterol, aggressive monkeys had less serotonin than the high-cholesterol monkeys.

Cholesterol is a major component of brain-cell membranes. Alterations in dietary cholesterol affect the fluidity and viscosity of the membranes, which house receptors for serotonin. So altering the condition of neuronal membranes may well alter the function of these serotonin receptors, explains Kaplan.

The findings, reported in Psycho-somatic Medicine (Vol. 56), raise questions about the National Cholesterol Education Program recommendations that Americans over the age of two significantly lower their intake of fat and cholesterol. "Can this diet do harm?" asks Kaplan. "For people who already have low serotonergic activity, a low-cholesterol diet might shove them across some threshold that makes them more likely to do things they might not otherwise do."

Or into depression. A recent study of men being treated for heart disease showed that those receiving cholesterol-lowering drugs experienced more symptoms of depression and anxiety than those who were not on the drugs.

Kaplan is swimming against a strong current. "The NIH," he laments, "has billions of dollars tied up in the [cholesterol] hypothesis."